08 Principles Indications and Limits

7/29/2019 08 Principles Indications and Limits

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7Principles for Breast Reconstruction:Indications and LimitsJennifer L. Marti and Virgilio Sacchini

7.1 Introduction

Breast cancer occurs in one of eight American women.

Although many patients are candidates for breast-conser-

vation therapy, the rates of mastectomy and of contralateral

risk-reducing mastectomy have risen in recent years in theUSA [1]. The vast majority of patients undergoing mas-

tectomy are candidates for breast reconstruction. Accord-

ingly, the number of breast reconstruction operations has

also increased [2].

Extensive literature clearly supports the advantages and

oncologic safety of reconstruction after mastectomy.

Reconstruction after mastectomy has been shown to be

effective in restoring body image, improving quality of life,

and reducing the psychological distress of mastectomy [3,

4]. At the same time, immediate reconstruction has been

found to be oncologically safe after mastectomy, even in

cases of advanced breast cancer [57]. This has been con-

clusively demonstrated in multiple studies, including a

meta-analysis by Gieni et al. [8], which confirmed no

increased risk of local recurrence with immediate breast

reconstruction after mastectomy. However, despite its

advantages and oncologic safety, fewer than 25 % of

American patients undergo immediate or delayed recon-

struction after mastectomy [9].

Options for reconstruction include reconstruction with

autologous tissue, or with a tissue expander and implant. For

unilateral reconstruction, symmetry is more easily obtained

with a tissue flap than with an implant [2]. Autologous flap

options include latissimus dorsi myocutaneous flaps,

transverse rectus abdominus myocutaneous (TRAM) flaps,

deep inferior epigastric perforator flaps, and gluteal artery

perforator flaps [3]. Implants contain either saline or silicone.

An immediate one-stage reconstruction with an implant may

be feasible; however, most patients undergo a staged proce-

dure with a tissue expander to allow for interval expansion,followed by an exchange to a permanent implant.

Autologous reconstruction may be difficult or compli-

cated in patients who have undergone prior surgery at

potential donor sites, or who have medical comorbidities

such as hypertension, diabetes, and chronic obstructive

pulmonary disease, who are smokers, or who are at the

extremes of body mass index [3].

7.2 Immediate Versus DelayedReconstruction

Most patients undergoing mastectomy are candidates for

immediate reconstruction. Immediate reconstruction offers

multiple advantages, including one-stage surgery, better

cosmetic outcome, and improved psychological state. In the

only randomized controlled trial to date comparing imme-

diate and delayed breast reconstruction, Dean et al. [10]

reported increased psychological well-being with immedi-

ate reconstruction [3]. Immediate reconstruction often

achieves a better aesthetic result than delayed reconstruc-

tion, owing to preservation of the skin envelope and infra-

mammary fold [11]. For patients who undergo delayed

reconstruction, use of an autologous flap is preferable to useof an implant, as the process of tissue expansion required

for an implant is difficult owing to skin stiffness, resulting in

a suboptimal cosmetic result [2]. A combination of a tissue

expander and an implant with a latissimus dorsi flap is

another option for breast reconstruction.

J. L. Marti

Department of Surgery, Beth Israel Medical Center,

New York, USA

e-mail: [email protected]

V. Sacchini (&)

Breast Service, Department of Surgery, Memorial Sloan-

Kettering Cancer Center, New York, USA

e-mail: [email protected]

C. Urban and M. Rietjens (eds.), Oncoplastic and Reconstructive Breast Surgery,DOI: 10.1007/978-88-470-2652-0_7, Springer-Verlag Italia 2013

77


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7.2.1 Breast Reconstruction Considerationswith Anticipated PostmastectomyRadiotherapy

Immediate reconstruction in patients who will undergoanticipated postmastectomy radiotherapy (PMRT) is con-

troversial. The two main issues that raise concern are

compromised delivery of radiotherapy in the face of a

reconstructed breast, and the impact of radiotherapy on the

long-term cosmetic result of the reconstruction [12].

7.2.2 Oncologic Safety of Reconstruction Priorto PMRT

Historically, delayed reconstruction has been recommended

when PMRT is planned. Some still advocate this approach,

owing to concerns of compromised delivery of radiotherapy

in the presence of a reconstructed breast, whether a tissue

flap or an implant [1216]. Concerns include compromised

delivery to the internal mammary lymph nodes, nonuniform

radiotherapy delivery, underdosing of the chest wall, and

increased radiotherapy dose to normal tissues with a breast

reconstruction in place [12]. The evidence is conflicting. On

the one hand, Motwani et al. [15] reported compromised

delivery of radiotherapy in 52 % of patients who had

undergone immediate reconstruction, compared with 7 % of

controls. However, Koutcher et al. [17] found no compro-

mised delivery of radiotherapy to the chest wall in most

patients, with an excellent 30-month actuarial locoregional

control rate of 97 %.Owing to concerns of compromised radiotherapy deliv-

ery attributable to the reconstructed breast, a delayed

immediate reconstruction algorithm is advocated at the

MD Anderson Cancer Center for patients who will receive

PMRT [2]. With this approach, a tissue expander is placed

at the time of mastectomy, and is deflated during adjuvant

radiotherapy (protocol outlined in Fig. 7.1). Tissue expan-

sion is performed after the completion of radiotherapy, and

reconstruction with an autologous flap is performed

46 months thereafter [18]. In this series, the approach

resulted in low complication rates, with tissue expander loss

in 14 % of patients. The recurrence rate at 32 months of

follow-up was low, at 3 % [18]. The complication rate with

a delayedimmediate approach with subsequent flap

reconstruction may be lower than that for a standard

delayed flap reconstruction (26 % vs. 38 %, p = 0.40) [18].

Despite the concerns about radiation delivery that

prompted development of the delayedimmediate

approach, many authors have reported acceptable recur-

rence rates and cosmetic outcomes with immediate recon-

struction followed by PMRT [17]. In one retrospective

Fig. 7.1 MD Anderson CancerCenter delayedimmediate breast

reconstruction protocol. LD

latissimus dorsi flap, PMRT

postmastectomy radiation

therapy, SGAP superior gluteal

artery perforator flap, TRAM

transverse rectus abdominus

myocutaneous flap. (Reprinted

with permission from Kronowitz

et al. [62])

78 J. L. Marti and V. Sacchini


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review of 191 patients requiring PMRT who underwent

TRAM flap reconstruction in either an immediate or a

delayed fashion, the risk of locoregional recurrence was not

significantly increased in the group undergoing immediate

reconstruction (3.7 % vs. 1.8 %, p = 0.65) at 40 months of

follow-up [19]. Similarly, Wright et al. [20] retrospectively

reviewed 104 patients who underwent exchange for a per-

manent implant prior to PMRT. Local control rates wereexcellent, 0 % at 5 years, and immediate reconstruction was

not associated with an elevated risk of distant metastases or

death.

In contrast to these data, others have reported higher

rates of locoregional recurrence among patients undergoing

immediate reconstruction. Nahabedian et al. [21] retro-

spectively analyzed 146 patients who underwent immediate

or delayed reconstruction after PMRT. Locoregional

recurrence rates were higher in patients who underwent

immediate versus delayed reconstruction (27 % vs. 15 %,

p = 0.04). These data should be interpreted with caution

because of the higher than expected rates of recurrence [21,

22]. As a result of these conflicting data, the safety of

immediate reconstruction prior to PMRT remains

controversial.

7.2.3 Effects of Radiotherapy on the CosmeticOutcome of the Reconstructed Breast

In addition to conflicting data about oncologic safety, there

is also debate about the impact of reconstruction prior to

PMRT on cosmetic outcomes. The main complications

caused by radiation on the reconstructed breast include fat

necrosis, impaired wound healing, contracture, fibrosis,

volume loss, and architectural distortion [23]. There are

data to support superior cosmetic results with delayed

reconstruction compared with immediate reconstruction.

Javaid et al. [23] in a systematic review of ten published

reports of patients undergoing immediate and delayed

reconstruction and PMRT found a higher incidence of

breast fibrosis and contracture with immediate reconstruc-

tion. Similarly, Kronowitz et al. [16], in a systematic review

of 49 articles, reported high rates of contracture and implant

loss among patients undergoing immediate reconstruction

prior to PMRT.

Other groups have also reported lower rates of compli-

cations after delayed reconstruction. Adesiyun et al. [24], in

a review of 113 patients who underwent immediate or

delayed breast reconstruction with PMRT, reported a lower

rate of complications in the delayed-reconstruction group

(32 % vs. 44 %, p = 0.18), although this difference was not

statistically significant. The patients general satisfaction

with their cosmetic outcome was similar in the two groups

(68 %) [24]. Another group found no significant difference

in complication rates with immediate or delayed recon-

struction with TRAM flaps in patients who received PMRT,

but the authors ultimately recommended delayed recon-

struction because of possible low power of the study [25].

Compared with the aforementioned studies, other groups

have reported acceptable cosmetic results and complication

rates with immediate reconstruction. A meta-analysis of 11

studies by Barry et al. [26] concluded that postoperativeoutcomes did not differ depending on whether reconstruc-

tion was performed before or after PMRT. Autologous flaps

appeared to have superior outcomes. Postoperative com-

plications such as fibrosis, contracture, infection, fat

necrosis, and reoperation were lower with autologous flap

reconstruction than with implant reconstruction [26]. Thus,

if immediate reconstruction is pursued, many authors

advocate reconstruction with an autologous flap over a tis-

sue expander/implant to enhance cosmetic results [6].

Although many authors have reported superior outcomes

with flap reconstruction compared with implant recon-

struction prior to PMRT, this does not necessarily imply

that successful outcomes cannot be achieved with implant

reconstruction. For example, Cordeiro et al. [27, 28]

reported satisfactory aesthetic results with immediate tissue

expander placement, followed by exchange for a permanent

implant prior to radiotherapy. Aesthetic results were cate-

gorized as good to excellent in 80 % of patients, with an

implant loss rate of 11 % [27].

7.2.4 Inflammatory Breast Cancer

In patients with inflammatory breast carcinoma, delayed

reconstruction is recommended because of extensive skin

involvement and a high risk of local recurrence [29]. The

required resection of skin precludes a skin-sparing mas-

tectomy. Furthermore, timely administration of radiother-

apy is imperative, making the delay for healing after

reconstruction undesirable. Therefore, reconstruction

should be delayed in patients undergoing mastectomy for

inflammatory breast cancer. This recommendation is

reflected in the 2012 National Cancer Comprehensive

Network guidelines [30].

There are two small series that have reported success

with immediate reconstruction. Chin et al. [31] performed a

retrospective analysis of 23 patients with inflammatory

breast cancer who underwent immediate or delayed recon-

struction. They reported similar rates of locoregional

recurrence (29 % vs. 33 %, p not significant), suggesting no

compromised oncologic outcome with immediate recon-

struction. Another small series found no overall survival

difference in patients who underwent immediate recon-

struction, although six of ten patients did develop local

recurrence [32]. Importantly, these small studies do not

7 Principles for Breast Reconstruction: Indications and Limits 79


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offer sufficient statistical power to conclusively demonstrate

the safety of immediate breast reconstruction for patients

with inflammatory breast cancer.

In conclusion, for patients who will likely require

PMRT, immediate reconstruction remains controversial,

owing to concerns of compromised radiotherapy delivery

and impaired cosmetic outcome of the reconstructed breast.

However, many authors have reported acceptable cosmeticoutcomes and comparable rates of locoregional recurrence

with immediate reconstruction. Immediate reconstruction is

not recommended in patients with inflammatory breast

cancer.

7.2.4.1 Nipple-Sparing Mastectomy

After a traditional skin-sparing mastectomy, patients may

subsequently undergo nipple reconstruction. This requires

an additional surgical procedure and tattooing, and ulti-

mately, many patients may never pursue this. Furthermore,

results may be disappointing. Jabor et al. [33] reported a

14 % rate of patient dissatisfaction after nippleareola

complex (NAC) reconstruction owing to loss of nipple

projection and the overall appearance and texture of the

reconstructed NAC. Therefore, preservation of the NAC

with a nipple-sparing mastectomy (NSM) may be desirable

in some patients.

Subcutaneous mastectomy with NAC preservation and

breast reconstruction was first described by Freeman [34] in

1962. Preservation of the NAC may enhance cosmetic

outcome and offer psychological benefit, as the NAC plays

an important role in the identification of a womans body

image [35]. Indeed, Boneti et al. [36] reported higher

patient cosmetic satisfaction in patients who had undergone

NSM as compared with skin-sparing mastectomy. There is

theoretical concern about the oncologic safety of this pro-

cedure owing to an inability to resect all of the retroareolar

ductal tissue.

7.2.5 Candidates for NSM

When selecting a candidate for NSM, one must consider the

risk of cancer involvement of the NAC, and the size and

degree of ptosis of the breast [37]. Candidates for NSM

include patients undergoing risk-reducing mastectomy.

Patients may pursue risk-reducing mastectomy because of

high-risk factors such as a strong family history, the pres-

ence or history of a contralateral breast tumor, lobular

carcinoma in situ, or previous radiation for Hodgkin lym-

phoma [38]. Selected patients with ductal carcinoma in situ

(DCIS) or invasive breast cancer may also be candidates for

NSM [38]. In appropriately selected patients, only 12 %

will have tumor involvement at the NAC, precluding

preservation [39, 40].

The factors associated with nipple involvement include

tumors larger than 24 cm, a tumornipple distance of less

than 2 cm, breast tumors overlapping more than one

quadrant, grade 3 or undifferentiated cancers, stage III

disease, human epidermal growth factor receptor 2 (HER2)/

neu positivity, and an extensive intraductal component of

greater than 25 % [4143].

For patients with invasive cancer, small tumors located

in the periphery of the breast have the lowest risk of NAC

involvement. The lowest risk of NAC involvement occurs

in tumors smaller than 2 cm, located at least 2.5 cm from

the NAC [44]. Tumors located within 2 cm of the NAC, or

larger than 4 cm, were found in one report to have occult

tumor present at the nipple in 50 % of cases [44]. A path-

ologic analysis of 140 mastectomy specimens reported a

16 % rate of NAC involvement with cancer. In all cases, the

primary tumor was located within 2.5 cm of the NAC [45].

Many series of carefully selected patients have reported

low rates of NAC involvement, ranging from 6 to 10 % [37,

38, 4649]. In one series of patients with peripheral tumors

and clinically node-negative disease, a low rate (less than

2 %) of NAC involvement was reported [48]. Therefore, the

risk of NAC involvement is lower in patients with low-

grade, unicentric, small, peripheral tumors, with clinically

uninvolved axillary lymph nodes, who have not undergone

neoadjuvant chemotherapy [39, 48, 50, 51]. Patients who

will likely undergo radiotherapy are not ideal candidates, as

they have advanced disease that portends a higher proba-

bility of NAC involvement. Furthermore, radiotherapy may

result in distortion and asymmetric displacement of the

NAC. A proposed algorithm for patient selection is illus-

trated in Fig. 7.2.

Fig. 7.2 Patient selectioncriteria for nipple-sparing

mastectomy. CA cancer, NAC

nippleareola complex.

(Reproduced with permission

from Spear et al. [50])



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7.2.6 Intraoperative Assessment of NAC TumorInvolvement

Identification of NAC tumor involvement precludes NAC

preservation. Intraoperative pathologic assessment with

frozen section of the retroareolar ducts can be useful to

identify the presence of NAC tumor involvement at the

initial surgery [39, 42, 52]. Dissection of the retroaerolarducts should be done sharply, as cautery can cause thermal

damage to the NAC [52]. Coring of the nipple ducts may be

facilitated by everting the nipple [52].

Frozen-section analysis is 91 % sensitive and 99 %

specific for assessing tumor involvement of the NAC [53].

Reported rates of positive frozen section range from 2.5 to

12 % in well-selected patients [36, 39, 54, 55]. With careful

patient selection and the use of preoperative MRI, Wi-

jayanayagam et al. [56] reported a low rate of NAC

involvement of 3 %. NAC tumor involvement may not be

identified until final surgical pathologic analysis, necessi-

tating NAC resection at a second surgery. When the NAC is

involved with tumor, the histologic finding is usually DCIS,

although atypical ductal hyperplasia and invasive breast

carcinoma may also be identified [39, 43, 54, 57].

7.2.7 Rates of Recurrence After NSM

Multiple series with less than 3 years of follow-up have

reported recurrence rates of 5 % or less after NSM, com-

parable to rates of recurrence after skin-sparing mastectomy

[36, 40, 55, 58]. Voltura et al. [55] reported a 5 % recur-

rence rate at 24 months in patients with aggressive triple-

negative tumors. Sacchini et al. [58] reported recurrences in

only two of 123 patients undergoing NSM, with a median

follow-up of 25 months. Recurrences did not occur at the

NAC [58]. Breast cancer occurred in two patients who

underwent risk-reducing mastectomies, located in periphe-

ral locations [58]. In another series of 96 patients who

underwent NSM with a median follow-up of 34 months,

only one patient developed a locoregional recurrence, and

two patients developed distant metastases [40].

The reported recurrence rates of longer-term studies,

with follow-up of at least 3 years, range from 5 to 28 % [39,

42, 59, 60]. In a review of 112 patients who underwent

NSM and had tumors located at least 2 cm from the nipple,

5 % of patients has recurrence at a mean follow-up of

59 months [42]. Recurrences occurred in the chest wall,

upper breast, and inframammary fold, with only one

recurrence in the NAC [42]. The location of these recur-

rences highlights the importance of considering the poten-

tial for elevated risk at the periphery of the breast after

NSM, as access to the peripheral breast may be more dif-

ficult if a small periareolar incision is used.

Studies with long-term follow-up of patients who

undergo NSM are limited, and have not definitively dem-

onstrated the long-term oncologic safety of NSM. In a series

with a follow-up of 5.5 years, Caruso et al. [59] reported a

recurrence rate of 12 % in 50 patients. Recurrences occur-

red at the NAC in one patient, and distant metastases

developed in four patients. In a prospective trial with a

median follow-up of 13 years, Benediktsson and Perbeck[53] reported a high overall locoregional recurrence rate of

28 %. This may suggest that NSM is not oncologically safe

in the long term, but this high rate may have been due to

patient selection. Patients at high risk of recurrence were

included, with tumors larger than 3 cm or multicentric

disease [53]. Patients in this study who received PMRT had

a local recurrence rate of 8.5 %, similar to reported rates

after skin-sparing mastectomy [53].

Petit et al. [60] recently published an update of their

experience with 934 patients who underwent NSM with a

median follow-up of 50 months. These investigators rou-

tinely treat the NAC intraoperatively with electron intra-

operative treatment if the frozen section is negative, and

preserve the NAC even if final pathologic investigation

reveals tumor involvement [60]. For patients with invasive

ductal cancer, 3.6 % had recurrence in the breast at 5 years,

and 0.8 % had recurrence at the NAC [60]. Of the patients

who had recurrence at the NAC, most had an extensive

intraductal component and had HER2/neu positivity [60].

For patients with DCIS, the rate of locoregional recurrence

at 5 years was high: 8 % [60]. The rate of recurrence was

4.9 % in the breast and 2.9 % at the NAC [60]. These high

recurrence rates may cause one to pause before offering this

procedure to patients with DCIS. Predictors of breast

recurrence among patients with DCIS included age under

40 years, positive retroareolar margins, estrogen receptor

negativity, progesterone receptor negativity, high-grade

histologic findings, HER2/neu positivity, and Ki-67 index

greater than 20 % [60].

In conclusion, several studies support the short-term

oncologic safety of NSM, with locoregional recurrence

rates similar to those of skin-sparing mastectomy, and rare

recurrences occurring at the NAC. However, the long-term

oncologic safety of this procedure has not been determined,

and the recent data of Petit et al. [60] may be a reason for

caution in patients with DCIS. More studies with longer-

term follow-up are needed, as the literature to date is not yet

definitive on the oncologic safety of NSM in the long term.

7.2.8 NSM in BRCA Mutation Carriers

The oncologic safety of NSM in BRCA mutation carriers is

controversial, as breast tissue connects with the nipple and

cannot be completely resected with NAC preservation [61].



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One pathologic analysis of mastectomy specimens of

BRCA patients revealed that terminal ductal lobular units

were present in 24 % of the NACs and 8 % of nipples [61].

The long-term potential of this retained tissue developing a

cancer is unknown [61]. In this study, occult NAC tumor

involvement was 0 % in risk-reducing specimens, and 10 %

in therapeutic specimens. These rates are similar to those

for non-BRCA mutation carriers [61]. Long-term studiesare needed before we can say with absolute certainty that

NSM is an oncologically sound procedure in BRCA

patients.

7.2.8.1 Postoperative Outcomes of the NAC

Patients should be counseled that the NAC preservation in

NSM is mainly of cosmetic, not functional benefit. Most

patients will not experience sustained preservation of nipple

sensation or erectile ability [39]. There is a risk of

approximately 12 % of occult tumor involvement at the

NAC, requiring resection [39, 40]. Furthermore, there is a

risk of partial or complete necrosis of the NAC in approx-

imately 411 % of patients [38, 39, 42, 54, 58]. Preserva-

tion of the blood supply to the NAC may be maximized by

use of a lateral incision, without a circumareolar extension.

Also, the NAC may ultimately settle in a displaced or

asymmetric position, with lateral displacement occurring in

67 % of cases in one series [54].

Numerous studies have demonstrated the short-term

oncologic safety of NSM in risk reduction, and in patients

with early-stage breast cancer. Larger studies with longer

follow-up are needed to definitely demonstrate that NSM

has locoregional recurrence rates comparable to those of

skin-sparing mastectomy. Ideal candidates for NSM should

have small tumors (less than 3 cm), located at least 2 cm

from the nipple, with clinically uninvolved axillary lymph

nodes, and without skin involvement [50]. Patients with

extensive DCIS are not good candidates for NSM because

of reported high rates of locoregional recurrence [60]. Use

of intraoperative frozen section can identify most patients

with occult NAC involvement. Preservation of the NAC

may enhance cosmetic outcome and overall patient

satisfaction.

7.3 Conclusions

Most patients are candidates for immediate breast recon-

struction after mastectomy. For patients who will require

PMRT, immediate reconstruction is controversial, but many

authors have reported acceptable cosmetic results and

locoregional recurrence rates with immediate reconstruc-

tion. NSM may be an attractive option for women for risk

reduction, or in selected patients with early-stage breast

cancer.

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08 Principles Indications and Limits

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